Interest in the pharmacogenetics of oxidative drug metabolism has grown rapidly in the past several years. It has been discovered that a genetic deficiency in oxidative drug metabolism exists in certain subjects which causes the subjects to act as a slow or poor metabolizer rather than a fast, efficient or extensive metabolizer of certain drugs. Several drugs have been used as probes for the assessment of oxidative drug metabolism deficiencies in subjects, including dextromethorphan, debrisoquine and sparteine. See, for example, Kupfer et al, "Dextromethorphan as a Safe Probe for Debrisoquine Hydroxylation Polymorphism", The Lancet (Sept. 1, 1984), pages 517-518; Roy et al, "Methoxyphenamine and Dextromethorphan as Safe Probes for Debrisoquine Hydroxylation Polyamorphism", The Lancet (Dec. 15, 1984), page 1393; Schmid et al, "Polymorphic Dextromethorphan Metabolism: Co-Segregation of Oxidative O-Demethylation with Debrisoquine Hydroxylation", Clinical Pharmacology and Therapeutics, Vol. 38, No. 6 (1985), pages 618-624; De Zeeuw et al, "Interindividual Differences in Dextromethorphan Kinetics in Man", Acta Pharmacologica et Toxicologica, Vol. 59, Supplement V (1986), page 44; and Kupfer et al, "Pharmacogenetics of Dextromethorphan O-Demethylation in Man", Xenobiotica, Vol. 16, No. 5 (1986), pages 421-433, for further details of previous studies in this regard.
Generally, pharmacogenetic screening using the aforementioned or other drugs as probes has been conducted by administering the probe drug to a subject and then quantitatively monitoring a body fluid containing metabolites of the probe drug. Known methods for analyzing body fluids such as urine containing the drug and its metabolites include gas chromatography and high performance liquid chromatography. Both gas chromatography and high performance liquid chromatography provide a quantitative indication of the relative amounts of the probe drug and the metabolites of the probe drug in the sampled body fluid. The gas chromatography and high performance liquid chromatography method are particularly suitable for determining the relative amounts of the substances. Reports of pharmacogenetic screenings using either gas chromatography or high performance liquid chromatography techniques are disclosed by, for example, Price Evans et al, Journal of Medical Genetics, 17 (1980), pages 102-105 (gas chromatography); Kupfer et al, European Journal of Clinical Pharmacology, 26 (1984,) pages 753-759 (gas liquid chromatograph); Wedlund et al, Clinical Pharmacology and Therapeutics, Vol. 36, No. 6 (1984), pages 773-780 (high performance liquid chromatography); Jurima et al, British Journal of Clinical Pharmacology, 19 (1985), pages 483-487 (gas chromatography); and Eichelbaum et al, Xenobiotica, Vol. 16, No. 5 (1986), pages 465-481 (gas chromatography).
Additionally, determinations of dextromethorphan and its metabolites using high pressure liquid chromatography suitable for use in pharmacogenetic screening procedures are disclosed by Park et al, Journal of Pharmaceutical Sciences, Vol. 73, No. 1 (1984), pages 24-29; Achari et al, Journal of Pharmaceutical Sciences, Vol. 73, No. 12 (1984), pages 1821-1822; and East et al, Journal of Chromatography, 338 (1985), pages 99-112.
While gas chromatography and high performance liquid chromatography are advantageous in providing quantitative analyses of oxidative drug metabolism during pharmacogenetic screening, these methods are disadvantageous in that they require complex, expensive equipment, including chromatographic columns, and in that they are time consuming. For example, in a typical arrangement, a high pressure liquid chromatography apparatus permits only one analysis per ten minute period. Thus, a need exists for a faster method of analysis in pharmacogenetic screening of oxidative drug metabolisms. A need also exists for such a method of analysis which uses more simple and inexpensive equipment than that required in the gas and high performance liquid chromatography techniques.